Patent review of 5,000+ oral GLP-1 drug candidates reveals key structural features for future non-injectable diabetes therapy | Research

The takeaway

Analysis of 67 patents (5,000+ compounds) reveals key SAR trends for danuglipron/lotiglipron-like oral GLP-1 agonists: carboxyl groups boost activity, bioisosteric replacements improve pharmacokinetics, and promising chemotypes suggest approved oral agents are achievable.

5,000+ oral GLP-1 candidates
Massive patent pipeline of danuglipron/lotiglipron-like oral small molecules with identified SAR trends suggests approved oral GLP-1 drugs are imminent

What the researchers found

67 patents; 5,000+ compounds analyzed; 2021-2024. SAR: carboxyl groups → high activity; bioisosteres → better ADME; privileged fragments identified; heterocycle replacements viable; piperidine modifications promising. Clinical: danuglipron/lotiglipron had issues but spawned robust pipeline.

Why it matters

The injection barrier limits GLP-1 drug adoption. Identifying SAR trends from 5,000+ oral candidates accelerates the development of non-injectable alternatives that could reach billions more patients.

How the study worked

Patent review of Espacenet and Google Patents databases (Jan 2021-Jul 2024). SAR analysis of danuglipron- and lotiglipron-like agonists. 67 publications, 5,000+ compounds.

What this study cannot tell us

Patent review—not clinical data. Most compounds are untested in humans. Complex GLP-1R signaling may limit small-molecule approaches. Biased signaling implications unknown.

How to read the evidence

Comprehensive patent SAR review. Chemical evidence, not clinical.

When this study was published

Published in 2025; patents 2021-2024.

The bigger picture

The oral GLP-1 pipeline is enormous—5,000+ compounds in just 3 years. This suggests oral GLP-1 drugs are not a question of "if" but "which one" and "when," potentially transforming diabetes and obesity treatment worldwide.

Questions still open

Which oral GLP-1 candidate will reach approval first?
Can small molecules achieve the same weight loss as injectable peptides?
Will oral GLP-1 drugs be cheaper than injectable versions?

Common questions

Will there be a GLP-1 pill for weight loss?

Very likely. This review analyzed over 5,000 oral GLP-1 drug candidates from 67 patents. While Pfizer's first attempts (danuglipron, lotiglipron) had issues, the enormous number of new candidates suggests an approved oral GLP-1 drug is achievable within a few years.

How are oral GLP-1 drugs different from injectable ones?

Injectable GLP-1 drugs are peptides (small proteins) that must be injected because they would be destroyed by digestion. Oral small-molecule agonists are traditional drug-like chemicals that survive digestion and activate the same GLP-1 receptor. Over 5,000 such molecules are now in development.

Read the original research

"Next-in-class" GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020-2024).

Current medicinal chemistry

View on PubMed ↗Publisher’s paper ↗

Citation

Tolkacheva, Elena V; Saliev, Alexandr Yu; Salakhov, Tagir L; Balakin, Konstantin V; Ivanov, Roman A; Chernyshov, Vladimir V. (2025). "Next-in-class" GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020-2024).. Current medicinal chemistry. https://doi.org/10.2174/0109298673366258250710101146